The obstructive sleep apnea syndrome (OSAS) is a significant cause of morbidity in children. Little is known about the pathophysiology of this common and important disease. We hypothesized that children with OSAS have abnormalities in their ventilatory drive and/or arousal responses, which contribute to upper airway obstruction. Initial data, which have now been published, showed that children with OSAS have blunted arousal responses to hyercapnia. In the second part of the protocol, arousal and ventilatory responses to inspiratory resistance loading (IRL) were tested. Children with OSAS aroused at a higher load than controls (23 + 8 vs 15 + 7 cm H2O/L/s, P < 0.05). Patients with OSAS had higher arousal thresholds during rapid eye movement (REM) vs nonREM sleep (P < 0.001), whereas normal subjects had lower arousal thresholds during REM (P < 0.005). Ventilatory responses to IRL were evaluated in the controls. There was a marked decrease in tidal volume both immediately (56 + 17% of baseline at an IRL of 15 cm H2O/L/min, P < 0.001) and after 3 minutes of IRL (67 + 23%, P < 0.005). The duty cycle increased. We conclude that children with OSAS have impaired arousal responses to IRL. Normal children have only partial ventilatory compensation for IRL during sleep. However, arousal occurs before IRL results in gas exchange abnormalities. The response in children differs from adults. We speculate that abnormal arousal responses to IRL may play a role in the pathophysiology of childhood obstructive sleep apnea.